AB0172 ANTI-MITOFUSIN-1 AND THROMBOSPONDIN-1 AS POTENTIAL MARKERS FOR POLYMYALGIA RHEUMATICA
Authors: L. Johansson, D. Michailidou, S. Rantapää Dahlqvist, C. Lood
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder characterized by aching and stiffness in the proximal regions of the extremities and elevated markers of inflammation. PMR and giant cell arteritis (GCA) are two conditions frequently coexisting [1,2], with increased incidence of large vessel vasculitis and aneurysm development found at long term follow-up. Furthermore, PMR can be one of the manifestations of GCA in 20-40% of cases [3]. The etiology of the diseases are still largely unknown, and specific serological markers, including to monitor arterial disease, are lacking. Recent studies have shown that mitochondrial dysfunction may play a central role in immune activation and could act as a potential source of antigens, including mitofusin-1 (MFN1), in autoimmune diseases [4,5,6]. <h3>Objectives</h3> To determine whether patients with PMR, with or without overlapping GCA, have elevated levels of markers of platelet activation (e.g. thrombospondin-1; TSP-1), and mitochondrial autoantibodies (e.g. anti-MFN1). <h3>Methods</h3> Plasma levels of anti-MFN-1 IgG and TSP-1 were measured in healthy controls (HC) (n=30) and patients with PMR (n=60), before and after treatment with glucocorticoids using in-house and commercial ELISAs, respectively. <h3>Results</h3> Plasma levels of anti-MFN-1 IgG and TSP-1 were elevated in patients with PMR, compared with HC, both before and after treatment with corticosteroids (p&lt;0.001). The highest levels of anti-MFN-1 and TSP-1 were found before treatment of corticosteroids (p&lt;0.001). Co-existence of GCA did not affect levels of either anti-MFN1 or TSP-1, nor treatment response to corticosteroids. Elevated levels of TSP-1 were found to be significantly elevated in patients with symptoms from hips/glutes (n=39) as compared to patients without these symptoms (n=13), median (P25-P75) 27.11 ug/mL (22.5-35.0) vs 19.6 ug/mL (14.1-27.9), p=0.046. Lower concentration of anti-MFN1 IgG was found in patients with symptoms from the spine (n=31) in comparison with those without symptoms from the spine (n=21), median (P25-P75) 0.37 U/mL (0.27-0.57) vs 0.54 U/mL (0.47-0.96), p=0.043. <h3>Conclusion</h3> Increased levels of anti-MFN-1 IgG and TSP-1 were found in PMR patients and decreased significantly after treatment with corticosteroids, although still significantly higher than HC. The highest concentration of TSP-1 was found in individuals with symptoms from hips/glutes. Increased concentrations of anti-MFN-1 and TSP-1 are suggested as novel biomarkers for PMR and further, could serve as potential biomarkers for treatment response. <h3>References</h3> [1]Michet CJ, Matteson EL. Polymyalgia rheumatica. BMJ. 2008 Apr 5;336(7647):765-9. [2]Brooks RC, McGee SR. Diagnostic dilemmas in polymyalgia rheumatica. Arch Intern Med. 1997 Jan 27;157(2):162-8. [3]Dejaco C et al. The spectrum of giant cell arteritis and polymyalgia rheumatica: revisiting the concept of the disease. Rheumatology (Oxford). 2017 Apr 1;56(4):506-515. [4]Clayton SA et al. Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis. Front Immunol. 2021 Apr 29;12:673916. [5]Barrera MJ et al. Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: Potential role in Sjögren's syndrome. Autoimmun Rev. 2021 Aug;20(8):102867. [6]Becker YLC et al. Identification of Mitofusin 1 and Complement Component 1q Subcomponent Binding Protein as Mitochondrial Targets in Systemic Lupus Erythematosus. Arthritis Rheumatol. 2022 Jul;74(7):1193-1203. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Linda Johansson: None declared, Despina Michailidou Consultant of: Advisory Board fees from ChemoCentryx., Grant/research support from: NIH grant award #5T32HL007028-44., Solbritt Rantapää Dahlqvist: None declared, Christian Lood Consultant of: Advisory board for Redd Pharma., Grant/research support from: Receives research funding from Eli Lilly, Gilead Sciences, Boehringer Ingelheim, Redd Pharma, Amytryx, Horizon Pharma, Pfizer, and Bristol Meyers Squibb.